It is hypothesized that inflammatory cells and cytokines in the tumor microenvironment have a role in the development of cancer. Virchow discovered leukocytes in tumor tissues, suggesting that there is a relationship between inflammation and cancer; inflammatory cytokines are correlated with DNA disruption, tumor suppressor genes inactivation, angiogenesis, tumor growth promotion, and metastasis [6, 16]. The inflammatory cells release substances that cause tumor vessel proliferation and sustenance and tissue remodeling, leading to more vessel formation [6, 16]. In a tumor microenvironment, neutrophils release Reactive Oxygen Species (ROS) and Reactive Nitrogen Species having mutagenic effects; furthermore, inducible Nitric Oxide Synthase (iNOS) release leads to DNA and tissue injury [17].
The interaction between platelets and cancer can promote the tumor’s ability to evade immune cells’ action, which does not result in the eradication of neoplastic cells and the arrest of the blood vessels, hence enhancing the survival and persistence of cancer cells [18, 19]. Platelets are comprised of P-selectin, Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), glycoprotein IIb/IIIa (GPIIb/IIIa), GPIb/IX, and GPVI which cause platelet and cancer cell adhesion, escaping immune function, and metastasis and the release of VEGF and PDGF causes tumor cell proliferation, vascular permeability, and the formation of new blood vessels. Furthermore, the release of Transforming Growth Factor Beta (TGF-β) results in cancer cell invasion and proliferation [19].
The link between PCa and inflammation is explored and studied in the literature. Atrophic epithelium with stromal changes was found in older patients’ prostate biopsy. In this area, it is observed that inflammatory cells have high proliferative capacity compared to the surrounding normal prostate tissue, known as Proliferative inflammatory Atrophy (PIA) which may progress to High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and early prostate adenocarcinoma [20, 21]. During inflammation, PIA is exposed to ROS; loss of protective agents against ROS might change PIA to HGPIN or prostate carcinoma [22]. According to a previous meta-analysis, a history of prostatitis increases the risk of PCa with an odds ratio of 1.6 [23]. Moreover, in another meta-analysis, there were associations between syphilis and gonorrhea and PCa [24].
Recently, various blood parameters (NLR, PLR, LMR, and MPV) [8, 9, 10, 11, 12, 13] have been utilized to predict the diagnosis of PCa, clinically significant PCa, and its outcomes. However using these blood parameters is still a matter of debate and controversial as different studies argued that they are unreliable in detecting PCa [14, 15].
In this study, we assessed the ability of PSA combined with NLR or PLR in detecting significant PCa. We found that NLR, PLR, PNLR, and PPLR were high in the GS ≥ 7 group (p < 0.05) and that combined markers are associated with high GS PCa using different models in the multivariate analysis.
Toriola et al. found that the elevated number of leukocytes increased the risk of death from PCa by 2.57 times [25]. In another study, an increase in NLR and PLR was associated with poor oncologic findings [8]. Kawahara et al. in a study including 810 men who underwent prostate biopsy with PSA between 4 and 10 ng/dl found NLR to be a risk factor of PCa [10]. Minardi et al. revealed that NLR is related to disease-free survival in PCa patients; however, no correlation was observed with GS [9]. In this study, we found that NLR and PLR alone or combined with PSA are associated with GS. In Korean patients with gray-zone PSA, NLR was associated with PCa detection and GS ≥ 4 + 3 cancer [11]. Adhyatma et al. discovered that prebiopsy PLR is valuable in detecting PCa [12]. Mehmet et al. reported that aggressive PCa is associated with NLR increase; however, they suggested that prostatitis limited the use of NLR in detecting PCa [13].
On the other hand, Vidal et al. found no associations of PCa outcomes among black or white patients [14]. Murray et al. reported that the PLR and systemic immune-inflammation index (SII, NLR combined with PLR) did not differentiate between BPH, indolent cancer, and clinically significant PCa [15].
This study had several limitations as follows. Our study is a nonrandomized retrospective study from a single institution with a small population sample. Thus, various biases might affect the detection of clinically significant PCa. Although the use of blood parameters with PSA had better specificity and PPV, the NPV was low. Thus, despite improving the detection of aggressive PCa, these parameters are still not ideal.